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The cortex in the mammalian brain is the most complex brain region that integrates sensory information and coordinates motor and cognitive processes. To perform such functions, the cortex contains multiple subtypes of neurons that are generated during embryogenesis. Newly born neurons migrate to their proper location in the cortex, grow axons and dendrites, and form neuronal circuits. These developmental processes in the fetal brain are regulated to a large extent by a great variety of factors derived from the mother - starting from simple nutrients as building blocks and ending with hormones. Thus, when the normal maternal environment is disturbed due to maternal infection, stress, malnutrition, or toxic substances, it might have a profound impact on cortical development and the offspring can develop a variety of neurodevelopmental disorders. Here we first describe the major developmental processes which generate neuronal diversity in the cortex. We then review our knowledge of how most common maternal insults affect cortical development, perturb neuronal circuits, and lead to neurodevelopmental disorders. We further present a concept of selective vulnerability of cortical neuronal subtypes to maternal-derived insults, where the vulnerability of cortical neurons and their progenitors to an insult depends on the time (developmental period), place (location in the developing brain), and type (unique features of a cell type and an insult). Finally, we provide evidence for the existence of selective vulnerability during cortical development and identify the most vulnerable neuronal types, stages of differentiation, and developmental time for major maternal-derived insults., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.